Selenomethionine inhibits IL-1β inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) expression in primary human chondrocytes.

Autor: Cheng AW, Stabler TV, Bolognesi M, Kraus VB, Cheng, A W M, Stabler, T V, Bolognesi, M, Kraus, V B
Zdroj: Osteoarthritis & Cartilage; Jan2011, Vol. 19 Issue 1, p118-125, 8p
Abstrakt: Objective: Several lines of evidence show that selenium (Se) has potential protective effects in osteoarthritis (OA), however the exact mechanism is still unclear. As interleukin-1β (IL-1β) is one of the key proinflammatory cytokines contributing to the progression in OA, we investigated the effect of Se in neutralizing the inflammatory effects of IL-1β on nitric oxide (NO) and prostaglandin E₂ (PGE₂) production, and the signaling pathways involved.Methods: Isolated primary human chondrocytes were pretreated with selenomethionine (SeMet) (0.5 μM SeMet) for 24 h then co-treated without or with IL-1β (10 pg/ml or 50 pg/ml) for another 24 h followed by RNA isolation. Gene expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) was determined by quantitative Real Time-Polymerase Chain Reaction. Culture media concentrations of NO and PGE₂ were determined by nitrite (NO₂⁻) assay and immunoassay respectively. For analysis of cell signaling pathways, chondrocytes were pretreated with SeMet then stimulated with IL-1β for 0-45 min. The activity of IL-1β signaling pathways was determined by Western blot screening of phosphorylation states of signal transduction proteins.Results: SeMet inhibited chondrocyte gene expression of IL-1β induced iNOS (31-54%, P=0.031) and COX2 (50-65%, P=0.031) with corresponding reductions in both NO (19-47%, P=0.031) and PGE₂ (24-32%, P=0.031) production. Pretreatment with SeMet attenuated IL-1β induced activation of p38 MAPK (39%, P=0.039) but not the extracellular signal-regulated kinase pathways (ERK) 1/2, c-Jun N-terminal kinases (JNK) or nuclear factor κB (NFκB).Conclusions: This study elucidates one potential protective mechanism of Se, namely through the alteration of cell signaling and downstream transcription of pro-inflammatory effects of IL-1β. [ABSTRACT FROM AUTHOR]
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